中国科学院长春应用化学研究所导师教师信息介绍简介-王晓辉

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王晓辉博士

研究员，博士生导师
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邮件：xiaohui.wang@ciac.ac.cn

简介

王晓辉博士，研究员，中国科学院长春应用化学研究所药物化学生物学课题组组长，英国皇家学会-牛顿高级学者，澳大利亚研究委员会纳米生物光子学中心Partner Investigator。其围绕毒品成瘾和神经病理性疼痛等脑科学和神经生物学问题，开展病理分子机理、生物物理化学和药物发现的研究；已发表科研论文50余篇，论文引用超2000次，过百次引用论文9篇，研究工作被Nature、PNAS、Science-Signaling等许多杂志和媒体报道。获得多项国内外著名奖励的肯定，其中包括中国药学会-赛诺菲青年生物药物奖(2015年)、Migraine Research Foundation Award (2015年)、ISN (International Society for Neurochemistry)-CAEN Award (2016年)、APSN (Asian Pacific Society for Neurochemistry) Young Investigator Award (2016年)、中国药理学会施维雅青年药理学家奖(2017年)和吉林省自然科学学术成果二等奖（2018年）。

学术兼职：亚太神经化学学会理事(APSN Council Member)；中国化学会生物物理化学专业委员会委员；中国毒理学会药物依赖性毒理学专业委员会委员；中国药物滥用防治协会合成毒品研究分会委员会委员。

研究内容

    药物成瘾机理研究和戒毒创新新药物研发
    基于结构的药物分子虚拟筛选以及药物与靶点作用机制的研究
    基于模式动物的表型药物发现
    跨膜结构域为靶点的分子探针和药物发现
    中药药理学和基于中药的创新药物发现
    生物无机化学
    转化研究

论文：

52. Yang M.; Liu Y.;Wang M.;Yang C.; Sun S.;Zhang Q.;Guo J.;Wang,X.*; Sun G.*;Peng, Y.*.(2019) Biomineralized Gd/Dy composite nanoparticles for enhanced tumor photoablation with precise T1/T2-MR/CT/ thermal imaging guidance.Chem. Eng.J.,Accepted

51. Wang, X.;⁠⁠Li⁠, H.;Liu⁠, Y.;Wu, H⁠;Wang⁠, H.;Jin, S.;⁠Lu, Y.⁠;Chang, S.⁠;Liu, R.⁠;Peng, Y.;Guo, Z.⁠,;Wang,X.* (2019) Velvet antler methanol extracts (MEs) protects against oxidative stress in Caenorhabditis elegans by SKN-1.Biomed. Pharmacother. Doi：10.1016/j.biopha.2019.109668

50. Peng, Y.; Zhang, X.; Zhang, T.;Grace, P.; Li, H.; Wang, Y.; Chen, H.; Watkins L.; Hutchinson M.; Yin H.; Wang X.*;（2019) Lovastatin inhibits Toll-like receptor 4 signaling in microglia by targeting its co-receptor myeloid differentiation protein 2 and attenuates neuropathic pain.Brain Behav Immun.82:432-444.

49. Wang,X.*; Northcutt, A.L.; Cochran, T.A.; Zhang, X.; Fabisiak, T.J.; Haas, M.E.; Amat, J.; Li, H.; Rice, K.C.; Maier, S.F; Bachtell, R.K.; Hutchinson, M.R.; Watkins, L.R. (2019) Methamphetamine activates Toll-like receptor 4 to induce central immune signaling within the ventral tegmental area and contributes to extracellular dopamine increase in the nucleus accumbens shell. ACS Chem. Neurosci., 10(8):3622-3634.

48. Wang,Y.; Peng, Y.; Zhang, B.; Zhang, X.; Li, H.; Wilson, A. J.; Mineev, K. S.; Wang, X.* (2019)Targeting trimeric transmembrane domain 5 of oncogenic latent membrane protein 1 using a computationally designed peptide. Chem. Sci., 10(32):7584-7590.

47. Zhang, X.; Peng, Y.; Grace, P.; Metcalf, M.; Wang, Y.; Zhang, T.;Wu, S.; Selfridge, B.; Portoghese, P.; Rice, K.; Watkins, L.; Hutchinson, M.; Wang, X.*(2019) Stereochemistry and innate immune recognition: (+)-Norbinaltorphimine enantioselectively targets myeloid differentiation protein 2 and inhibits Toll-like receptor 4 signaling. FASEB J., 33(8):9577-9587.

46. Li, Y.; Li, H.; Zhao, L.*; Wang, X.*(2019) Effect of anti-oxidant property of short branched-chain fatty acids in caenorhabditis elegans. Chin. J. Biochem. Mol. Biol., 35, 404-412.

45. Li, H.; Wang, K.; Yao, J.; Liu, Z.; Zhou, H.; Wang, X.*(2019) Research progress in the development of nicotine as a medicine. Prog. Pharm. Sci., 43, 824-831.

44. Du, Z; Gao, N; Wang, X, Ren, J.; Qu, X.(2018). Near-Infrared switchable fullerene-based synergy therapy for alzheimer’s disease. Small, 14, 1801852.

43. Peng, Y.; Wang, X.* . (2018) Kineret protein solution survives ten years. J. Pharm. Biomed. Anal., 160, 383-385.

42. Zhang, X.; Cui, F.* ; Chen, H.; Zhang, T.; Wang, Y.; Jiang, Z.; Yang, K.; Rice, K. C.; Linda, L. R.; Hutchinson, M. R.; Li, Y.; Peng, Y. and Wang, X.* (2018) Dissecting the innate immune recognition of opioid inactive isomer (+)-naltrexone derived Toll-like receptor 4 (TLR4) antagonists. J. Chem. Inf. Model., 58, 816-825

41.Grace, P. M.#; Wang, X.#; Strand, K. A.; Baratta, M. V.; Zhang, Y.; Galer, E. L.; Yin, H.; Maier S. F.; Watkins, L. R. (2018) DREADDed microglia in pain: Implications for spinal inflammatory signaling in male rats. Exp. Neurol., 304, 125-131. (#These authors contribute equally to this work)

40. Guan, Y.; Du, Z.; Gao, N.; Cao, Y.; Wang, X.; Scott, P.; Song, H.; Ren, J.; Qu, X. (2018) Stereochemistry and amyloid inhibition: Asymmetric triplex metallohelices enantioselectively bind to Aβ peptide. Sci. Adv., 4, eaao6718.

39. Zhang, X.; Zhang, T.; Cui, F.; Li Y.; Peng Y.; Wang X.* (2016) Small molecule modulators of Toll-like receptor 4.Chin. J. of Appl. Chem., 33, 876-886.

38. Grace, P. M.; Strand, K. A.; Galer, E. L.; Urba, D. J.; Wang, X.; Baratta, M. V.; Fabisiak, T. J.; Anderson, M. D.; Chen, K.; Greene, L. I.; Berkelhammer D.; Zhang, Y.; Ellis, E. L.; Yin, H.; Campeau, S.; Rice, K. C.; Roth, B. L.; Maier, S. F.; Watkins, L. R. (2016) Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation. Proc. Natl. Acad. Sci. USA, 113, E3441-E3450.

37. Zhang, T.#; Peng, Y.#; Wang, X.*. (2016) Drug discovery for treating drug addiction by targeting glia, Prog. Pharm. Sci., 39, 56-61(#These authors contribute equally to this work; *Corresponding author; Invited review)

36. Wang, X.*; Zhang, Y.; Hutchinson, M. R.; Rice, K. C.; Yin, H.; Watkins, L. R. (2016) Pharmacological characterization of the opioid inactive isomers (+)-naltrexone and (+)-naloxone as Toll-like receptor 4 antagonists. Br. J. Pharmacol., 173, 856-869.

35. Selfridge, B. R.#; Wang, X.#; Zhang, Y.; Yin, H.; Watkins, L. R.; Jacobson, A. E.; Rice, K. C. (2015) Structure activity relationships of (+)-naltrexone-inspired Toll-like receptor 4 (TLR4) antagonists. J. Med. Chem., 58, 5038–5052. (#These authors contribute equally to this work)

34. Grace, P.; Wang, X.; Urban, D.; Baratta, M.; Galer, E.; Strand, K.; Zhang, Y.; Yin, H.; Roth, B.; Maier, S.; Watkins, L. R. (2015) Selective manipulation of spinal microglia by chemogenetics: implications for allodynia and inflammatory signaling. J. Pain, 4 , S38

33. Smith, C.#; Wang, X.#; Yin, H. (2015) Caspases come togetherover LPS. Trends Immunol., 36, 59-61. (#These authors contribute equally to this work)

32. Wang, X.; Wang, X.; Feng, Y.; Zhu, M.; Yin, H.; Guo, Q.; Meng, X. (2015) A two-photon fluorescent probe for detecting endogenous hypochlorite in living cells. Dalton Trans., 44, 6613-6619.

31. Yang, H.#; Chen, Y. Z.#; Zhang, Y.#; Wang, X.; Zhao, X.; Godfroy, J. I.; Lian, Q.; Zhang, M.; Zhang, T.; Yuan, Q.; Royal, M. A.; Driscoll, M.; Xia, N. S.; Yin, H.; Xue, D. (2015) A Lysin-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition and removal of apoptotic cells. Nat. Commun., 6, 5717. (# These authors contribute equally to this work)

30. Bachtell, R.; Hutchinson, M. R.; Wang, X. ; Rice, K. C.; Maier, S. F,; Watkins, L. R. (2015) Targeting the Toll of drug abuse: the translational potential of Toll-like receptor 4. CNS Neurol. Disord. Drug Targets., 14, 692-699.

29. Northcutt, A. L.; Hutchinson, M. R.#; Wang, X.#; Baratta, M.; Hiranita, T.; Cochran, T.; Pomrenze, M.; Galer, E.; Kopajtic, R.; Li, C. M.; Amat, J.; Larson, G.; Cooper, D.; Huang, Y.; O’Neil, C.; Yin, H.; Zahniser, N.; Katz, J.; Rice, K. C.; Maier, S. F.; Bachtell, R.; Watkins, L. R. (2015) DAT isn’t all that: cocaine reward and reinforcement requires Toll like receptor 4 signaling. Mol. Psychiatry, 20, 1525-1537.(#These authors contribute equally to this work)

28. Grace, P. M.; Ramos, K. M.; Rodgers, K. M.; Wang, X.; Hutchinson, M. R.; Lewis M. T.; Morgan, K. N.; Kroll, J. L.; Taylor, F. R.; Strand, K. A.; Zhang, Y.; Berkelhammer, D.; Huey, M.; Greene, L. I.; Cochran, T. A.; Yin, H.; Barth, D. S.; Johnson, K. W.; Rice, K.; Maier, S. F.; Watkins, L. R. (2014) Activation of adult rat CNS endothelial cells by opioid-induced TLR4 signaling induces proinflammatory, biochemical, morphological, and behavioral sequelae. Neuroscience, 280, 299-317.

27. Wang, X.; Cochran, T. A.; Hutchinson, M. R.; Yin, H.; Watkins, L. R. (2014) “Drug addiction” in Microglia in health and disease (Sierra, A.; Tremblay, M. E. Ed.), Springer-Verlag (Berlin Heidelberg), 299-317.

26. Watkins, L. R.; Wang, X.; Mustafa, S.; Hutchinson, M. R. (2014) In vivo veritas:(+)-naltrexone’s actions define translational importance. Trends Pharmacol. Sci., 35, 432-433

25. Wang, X., Smith, C.; Yin, H. (2013) Targeting Toll-like receptors with small molecule agents. Chem. Soc. Rev., 42, 4859-4866. (Cover article)

24. Wang, X.; Grace, P. M.; Pham, M. N.; Cheng, K.; Strand, K. A.; Smith, C.; Li, J.; Watkins, L. R.; Yin, H. (2013) Rifampin inhibits Toll-like receptor 4 signaling by targeting myeloid differentiation protein 2 and attenuates neuropathic pain. FASEB J., 27, 2713-2722

23. Li, J.#; Wang, X.#; Zhang, F.; Yin, H (2013) Toll-like receptors as the therapeutic targets of autoimmune connective tissue diseases. Pharmacol. Ther., 138, 441-45 (#These authors contribute equally to this work)

22. Wang, X.; Saludes, J. P.; Zhao, T. X.; Csakai, A.; Fiorini, Z.; Chavez, S. A.; Li, J.; Lee, G. I.; Varga, K.; Yin, H. (2012) Targeting the lateral interactions of transmembrane domain 5 of Epstein–Barr virus latent membrane protein 1. Biochim. Biophys. Acta-Biomembranes, 1818, 2282-2289.

21. Wang, X.; Fiorini, Z.; Smith T.; Zhang, Y.; Li, J.; Watkins, L. R.; Yin, H. (2012) Repositioning antimicrobial agent pentamidine as a disruptor of the lateral interactions of transmembrane domain 5 of EBV latent membrane protein 1. PLoS One, e47703

20. Wang, X.; Loram, L. C.; Ramos, K.; de Jesus, A. J.; Jacob, A. J.; Cheng, K.; Reddy, A.; Somogyi, A. A.; Hutchinson, M. R.; Watkins, L. R.; Yin, H. (2012) Morphine activates neuroinflammataion in a parallel manner to endotoxin. Proc. Natl. Acad. Sci. USA, 109, 6325-6330.

19. Cheng, K.; Wang, X.; Zhang, S.; Yin, H. (2012) Discovery of small molecule inhibitors of the TLR1-TLR2 complex. Angew. Chem. Int. Edit., 51, 12246-12249.

18. Zhang, S.; Cheng, K.; Wang, X.; Yin, H. (2012) Selection, synthesis, and antiinflammatory evaluation of the arylidenemalonate derivatives as TLR4 signaling inhibitor. Bioorg. Med. Chem., 20, 6073-6079. (Cover article).

17. Hutchinson, M. R.; Northcutt, A. L.; Hiranita, T.; Wang, X.; Lewis, S.; Kopajtic, T. A.; Loram, L.; Sfregola, C.; Galer, E.; Miles, N. E.; Bland, S. T.; Amat, J.; Rozeske, R. R.; Maslanik, T.; Chapman, T.; Strand, K.; Fleshner, M.; Bachtell, R. K.; Yin, H. J.; Katz, L.; Rice, K. C.; Maier, S. F.; Watkins, L. R. (2012) Opioid activation of Toll-Like receptor 4 contributes to drug reinforcement. J. Neurosci., 32, 11187-11200.

16.Cheng, K.; Wang, X.; Yin, H. (2011) Small molecule inhibitors of the TLR3/dsRNAcomplex. J. Am. Chem. Soc., 133, 3764-3767.

15. Wang, X.; Qu, K.; Xu, B.; Ren, J.; Qu, X. (2011) Microwave assisted one-step green synthesis of multicolorphotoluminescentcarbondots without surface passivation reagents. J. Mater. Chem., 21, 2445-2450.

14. Wang, X.; Qu, K.; Xu, B.; Ren, J.; Qu, X. (2011) Multicolor luminescent carbon nanoparticles: synthesis, supramolecularassembly with porphyrin, intrinsic peroxidase-like catalytic activity and application. Nano. Res., 4, 908-920.

13. Wang, X.; Ren, J.; Miyoshi, D.; Sugimoto, N.; Qu, X. (2011) Label-free colorimetric and quantitative detection of cancer marker protein using noncrosslinking aggregation of Au/Ag nanoparticles induced by target-specific peptide probe. Biosens. Bioelectron., 26, 4804-4809.

12. Wang, X.; Chen, Y.; Ren, J.; Qu, X. (2011) Small interfering RNA for effective cancer therapies. Mini. Rev. Med. Chem., 11, 114-124.

11.Song, Y.; Wang, X.; Zhao, C.; Qu, K.; Ren, J.; Qu, X. (2010) Label-free colorimetric detection of single nucleotide polymorphism by using single-walled carbon nanotube intrinsic peroxidase-like activity. Chem. Eur. J., 16, 3617-3621.

10. Wang, X.; Geng, J.; Miyoshib,D.; Ren, J.; Sugimoto, N.; Qu, X. (2010) A rapid and sensitive “add-mix-measure” assay for multiple proteinases based on one gold nanoparticle–peptide–fluorophore conjugate. Biosens. Bioelectron., 26, 743-747.

9. Wang, X.; Wang, C.; Qu, K.; Song, Y.; Ren, J.; Miyoshi, D.; Sugimoto, N.; Qu, X. (2010). Ultrasensitive and selective detection of a prognostic indicator in early-stage cancer using graphene oxide and carbon nanotubes. Adv. Funct. Mater., 20, 3967-3971.

8. Peng, Y.; Wang, X.; Xiao, Y.; Feng, L.; Zhao, C.; Ren. J.; Qu, X. (2009) An i-motif quadruplex DNA-based biosensor for distinguishing single- and multi-walled carbon nanotubes. J. Am. Chem. Soc., 131, 13813-13818.

7. Wang, X.; Song, Y.; Ren, J.; Qu, X. (2009) Knocking-down cyclin A2 by siRNA suppresses apoptosis and switches differentiation pathways in K562 cells upon administration with doxorubicin. PLoS One, 4, e6665.

6. Yu, H.; Wang, X.; Fu, M.; Ren, J.; Qu, X. (2008) Chiral metallo-supramolecular complexes selectively recognize human telomeric G-quadruplex DNA. Nucleic Acids Res., 36, 5695-5703.

5. Shi, Q.; Wang, X.; Ren, J. (2008) Biophysical characterization of the interaction of p21 with calmodulin: a mechanistic study. Biophys. Chem., 138, 138-143.

4. Wang, X.; Ren, J.; Qu, X. (2008) Targeted RNA interference of cyclin A2 mediated by functionalized single-walled carbon nanotubes induces proliferation arrest and apoptosis in chronic myelogenousleukemia K562 cells. Chem. Med. Chem., 3, 940-945.

3. Wang, X.; Ren, J.; Qu, X. (2008) Biophysical studies on the full-length human cyclin A2: protein stability and folding/unfolding thermodynamics. J. Phys. Chem. B, 112, 8346-8353.

2.Bao, H.; Wang, X.; Yu, H.; Fu, M.; Qu, X.; Zheng, Y.; Ren, J. (2007) Physical and spectral characterization of the human cyclin A gene and its interactions with anthracycline anticancer drugs. Chem. Phys. Lett., 436, 252-257.

1. Wang, X.; Fu, M.; Ren, J.; Qu, X. (2007) Evaluation of different culture conditions for high-level soluble expression of human cyclin A2 with pET vector in BL21 (DE3) and spectroscopic characterization of its inclusion body structure. Protein Expr. Purif., 56, 27-34.

专利

1. 王晓辉, 张晓铮. 二元纳曲酮衍生物的应用: 中国, 201811405660.2[P]. 2018-11-23

2. 王晓辉, 张晓铮洛伐他汀在制备小胶质细胞活化抑制剂中的应用: 中国, 201910470041.X[P]. 2019-05-31

科研项目
    1、国际
    Granting Agency: Royal Society-Newton Advanced Fellowship, UK；Title: Peptide Based TLR4 Chemical Probe Development for Inhibition of the TLR4/MD-2 interaction
    2、国家自然科学基金
    Granting Agency: National Natural Science Foundation of China；Title: Innate immune recognition of Toll-like receptor 13
    Granting Agency: National Natural Science Foundation of China；Title: Role of gycosylation in dsRNA recognition of TLR3 via molecular dynamics simulation
    Granting Agency: National Natural Science Foundation of China；Title: Drug addiction therapy by targeting TLR4/MD-2
    Granting Agency: National Natural Science Foundation of China；Title: Construction of multivalent chiral molecular library with opioid molecular scaffold and its chiral recognition and regulation of innate immune receptor TLR4
    3、国家科学技术部
    Granting Agency: The National Key Research and Development Program of China；Title: Drug discovery for treating drug addiction by modulating microglia
    4、中国科学院